Background Previous studies have suggested a link between Sleep Disordered Breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, and the ApoE alleles. Methods 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (P-Tau), total-tau (T-Tau), and amyloid beta 42 (Aβ42), as well as ApoE allele status. Findings In ApoE3+ subjects, significant differences were found between sleep groups for P-Tau (F[df2]=4.3, p=0.017), and T-Tau (F[df2]=3.3, p=0.043). Additionally, among ApoE3+ subjects, the apnea/hypopnea with 4% O2-desaturation index (AHI4%) was positively correlated with P-Tau (r=0.30, p=0.023), T-Tau (r=0.31, p=0.021), and Aβ42 (r=0.31, p=0.021). In ApoE2+ subjects, AHI4% was correlated with lower levels of CSF Aβ42 (r=−0.71, p=0.004), similarly to ApoE4+ subjects where there was also a trend towards lower CSF Aβ42 levels Interpretation Our observations suggest that there is an association between SDB and CSF AD- biomarkers in cognitively normal elderly. Existing therapies for SDB such as CPAP could delay the onset to mild cognitive impairment or dementia in normal elderly.

Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013;36(3):405-412.

Compelling evidence shows that brown and beige adipose tissue are protective against metabolic diseases1,2. PR domain-containing 16 (PRDM16) is a dominant activator of the biogenesis of beige adipocytes by forming a complex with transcriptional and epigenetic factors and is therefore an attractive target for improving metabolic health3–8. However, a lack of knowledge surrounding the regulation of PRDM16 protein expression hampered us from selectively targeting this transcriptional pathway. Here we identify CUL2–APPBP2 as the ubiquitin E3 ligase that determines PRDM16 protein stability by catalysing its polyubiquitination. Inhibition of CUL2–APPBP2 sufficiently extended the half-life of PRDM16 protein and promoted beige adipocyte biogenesis. By contrast, elevated CUL2–APPBP2 expression was found in aged adipose tissues and repressed adipocyte thermogenesis by degrading PRDM16 protein. Importantly, extended PRDM16 protein stability by adipocyte-specific deletion of CUL2–APPBP2 counteracted diet-induced obesity, glucose intolerance, insulin resistance and dyslipidaemia in mice. These results offer a cell-autonomous route to selectively activate the PRDM16 pathway in adipose tissues.

S C I E N T I F I C I N V E S T I G A T I O N SU ntreated obstructive sleep apnea/hypopnea syndrome (OSAHS) signifi cantly affects quality of life and cardiovascular/cerebrovascular morbidities and mortality.1-4 CPAP therapy has been shown to be effective in treating sleep disordered breathing (SDB) by reducing the apnea/hypopnea index (AHI) 5 and by reducing excessive daytime somnolence (EDS). 6Despite this, CPAP acceptance and adherence are disappointingly low. A signifi cant number of patients (ranging from 30% to 80% in various studies) demonstrate an average CPAP usage of less than 4 hours per night. 7,8 Several reviews have emphasized the need to identify patients who are at the greatest risk for non-adherence, with the goal of developing techniques to maximize overall adherence. 9,10Studies have suggested that CPAP adherence can be correlated to characteristics of patients at baseline, such as the severity of OSAHS, 11-13 the level of EDS, 14 and anatomical factors (smaller nasal cross-sectional area, reduced nasal volume, and high nasal resistance 15,16 ), but the strength of these correlations has been weak. Drake et al. showed that patients whose sleep effi ciency on the CPAP titration night improved most had the greatest CPAP compliance at 47 days.17 More recently, studies using social cognitive theory 18-20 and health BRIEF SUMMARYCurrent knowledge/Study Rationale: Despite its efficacy, adherence to CPAP therapy is highly variable amongst patients with obstructive sleep apnea with large numbers of patients demonstrating inadequate adherence to CPAP. The present study is aimed at identifying early predictors of CPAP adherence from variables obtained at the time of diagnosis and titration of CPAP, thereby providing potential for early intervention. Study Impact: Our data show that better sleep quality (greater % REM) was seen in patients with higher CPAP adherence and confi rm that long term adherence was largely predicted by short term adherence. This suggests that interventions that improve sleep during or prior to the CPAP titration study may be useful in improving CPAP adherence.